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Asymmetric Synthesis of Nortropanes via Rh-Catalyzed Allylic Arylation.

ABSTRACT: Tropane derivatives are extensively used in medicine, but catalytic asymmetric methods for their synthesis are underexplored. Here, we report Rh-catalyzed asymmetric Suzuki-Miyaura-type cross-coupling reactions between a racemic N-Boc-nortropane-derived allylic chloride and (hetero)aryl boronic esters. The reaction proceeds via an unexpected kinetic resolution, and the resolved enantiopure allyl chloride can undergo highly enantiospecific reactions with N-, O-, and S-containing nucleophiles. The method was applied in a highly stereoselective formal synthesis of YZJ-1139(1), a potential insomnia treatment that recently completed Phase II clinical trials. Our report represents an asymmetric catalytic method for the synthesis of YZJ-1139(1) and related compounds.

SUBMITTER: Zhang Y

PROVIDER: S-EPMC9361292 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Asymmetric Synthesis of Nortropanes via Rh-Catalyzed Allylic Arylation.

Zhang Yan Y Goetzke F Wieland FW Christensen Kirsten E KE Fletcher Stephen P SP

ACS catalysis 20220712 15

Tropane derivatives are extensively used in medicine, but catalytic asymmetric methods for their synthesis are underexplored. Here, we report Rh-catalyzed asymmetric Suzuki-Miyaura-type cross-coupling reactions between a racemic N-Boc-nortropane-derived allylic chloride and (hetero)aryl boronic esters. The reaction proceeds via an unexpected kinetic resolution, and the resolved enantiopure allyl chloride can undergo highly enantiospecific reactions with N-, O-, and S-containing nuc ...[more]

PMID: 35966601

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